title: A role for opioid system in the proconvulsant effects of sildenafil on the pentylenetetrazole-induced clonic seizure in mice.
abstract: There are several lines of evidence that opioidergic and nitrergic systems could modulate the seizure threshold. We previously have shown that sildenafil had proconvulsant effects in a model of clonic seizure induced by pentylenetetrazole (PTZ) or bicuculline. In the present study, we examined whether the opioid system participates in the action of sildenafil on the PTZ-induced clonic seizures in mice. Sildenafil (1, 5, 10 and 20 mg/kg, i.p.) significantly decreased the seizure threshold in a dose-dependent manner, whereas morphine had both anticonvulsant and proconvulsant effects at low (0.5, 1, and 3 mg/kg, s.c.) and high (60 mg/kg, s.c.) doses. A sub-effective dose of sildenafil (5 mg/kg) combined with a dose of morphine (7.5 mg/kg) which was sub-effective for its proconvulsant effects significantly decreased the seizure threshold. Although naltrexone at 0.5 and 1 mg/kg had no effect on the seizure threshold, it significantly prevented both the proconvulsant effects of sildenafil as well as the anticonvulsant and proconvulsant effects of morphine on the PTZ-induced seizure thresholds. Our data suggested a role for opioidergic system in the proconvulsant effects of sildenafil on the PTZ-induced clonic seizures in mice.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P.O. Box 13145-784, Tehran, Iran.
authors.forename: Laleh
authors.initials: L
authors.lastname: Montaser-Kouhsari
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.forename: Taha
authors.initials: T
authors.lastname: Gholipour
authors.forename: Pouya
authors.initials: P
authors.lastname: Ziai
authors.forename: Pooneh
authors.initials: P
authors.lastname: Nabavizadeh
authors.forename: Abbas
authors.initials: A
authors.lastname: Ghasemi
authors.forename: Arash
authors.initials: A
authors.lastname: Bahremand
authors.forename: Mehdi
authors.initials: M
authors.lastname: Ghasemi
authors.forename: Ahmad Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008297:Male; D051379:Mice; D009020:Morphine / Q000627:therapeutic use* / Q000633:toxicity; D018847:Opioid Peptides / Q000502:physiology*; D010433:Pentylenetetrazole / Q000633:toxicity*; D010879:Piperazines / Q000633:toxicity*; D011687:Purines / Q000633:toxicity; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000633:toxicity*
chemical_list: D000701:Analgesics, Opioid; D018847:Opioid Peptides; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D009020:Morphine; D000068677:Sildenafil Citrate; D010433:Pentylenetetrazole